The Dangers of Grapefruit Juice Interacting with Drugs

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Photo By Mother Earth Living staff
There are real dangers of grapefruit juice tnteracting with drugs.

Learn about the dangers of grapefruit juice interacting with drugs.

Grapefruit Juice Interacting with Drugs

Our bodies have a remarkable ability to process
foreign compounds. Consider the massive number of medications that
have been introduced in the past fifty years. These pharmaceutical
agents have many diverse actions such as treating cancer,
menopausal symptoms, infections, inflammation, pain, anxiety,
seizures, high blood pressure, and high cholesterol, just to name a
few. It’s a wonder that chemicals designed in a laboratory could
have such powerful and pervasive biochemical effects on our
physiology. And it is perhaps equally wondrous that we manufacture
an elaborate set of enzymes that allows us to take drugs in precise
doses over extended periods of time without developing intolerable
side effects. These enzymes accomplish this feat by metabolizing
the drugs so that they can be eliminated from our bloodstream and
tissues before they become toxic.

There is only one catch to this elegant garbage disposal
system—it is prone to clogging. In modern cultures, human beings
typically eat a complex diet that includes a wide variety of foods
and spices. In addition, the trend toward medical self-care has led
us to consume a growing number of herbal medicines. Foods and herbs
contain a vast array of naturally occurring chemicals—too many to
count—that are also processed by the very same enzymes that
metabolize drugs, hormones, and toxins. This massive influx of
chemicals burdens the disposal system, placing it at risk of
overloading. As a consequence, the more new drugs we introduce into
our bodies, the more likely we are to encounter significant
interactions between these drugs, the foods we eat, and botanical

The Case of Grapefruit Juice and Drugs

A case in point is grapefruit, an extremely popular and
nutritious food. Surveys have shown that up to 21 percent of all
households in the United States purchase grapefruit juice. For most
consumers, this is probably a very good thing—there are substances
in grapefruit that appear to help prevent both cancer and heart
disease. However, grapefruit juice also has a unique property: It
can raise the blood levels of numerous prescription medications.
Because grapefruit juice is usually consumed with breakfast—the
same time that many people take their medications—this increases
the likelihood of a significant effect. Depending on the condition
being treated and the relative safety of the drug involved, this
interaction could potentially be a problem . . . or, it could also
be a benefit.

Almost ten years ago, a medical study was conducted to
investigate the effect of alcohol on the absorption of a blood
pressure medicine called felodipine. As part of the study,
grapefruit juice was added to mask the taste of the alcohol. Much
to the investigators’ surprise, it was discovered that the addition
of grapefruit juice markedly enhanced the absorption of felodipine
and raised its concentration in the bloodstream. In the years that
followed, a similar effect was found with numerous other
medications, and extensive research was conducted to find out
exactly how this interaction occurred.

A central component of the body’s drug detoxification system is
a family of enzymes called the cytochrome P450, or CYP450. These
enzymes are found throughout the body but are especially
concentrated in the liver and the walls of the intestines. The role
of these CYP450 enzymes is to alter the chemical structure of a
drug (or hormone or toxin) so that it can be more rapidly
eliminated. When certain CYP450s are blocked or inhibited, the
effect is to slow down the elimination of that substance, thus
raising its level in the blood.

Grapefruit juice has been shown to inhibit a very specific
enzyme, the CYP3A4. In the intestinal walls, this enzyme makes up
70 percent of all of the CYP450s, and this is precisely where
grapefruit juice exerts its effect. In studies where purified
grapefruit juice was given intravenously, it did not influence the
blood levels of simultaneously administered medications. These
studies confirmed that the juice had to be taken by mouth for it to
impact drug metabolism. Further research found that a single,
200-ml cup of juice (about 7 fluid ounces) was sufficient to
inhibit the CYP3A4 enzyme by almost 50 percent for a full
twenty-four hours. Drinking a glass of grapefruit juice every day
for several weeks may reduce this effect slightly (to about 30
percent inhibition), but this is still significant.

Grapefruit and the Affected Drugs

The reason it has been important to gather this information in
so much detail is that CYP3A4 is a crucial enzyme for the
detoxification of many important drugs, possibly up to 50 percent
of all pharmaceutical agents. Anything that interferes with its
function can potentially amplify the activity of these drugs. The
list of drugs impacted is long but includes cyclosporine and
tacrolimus, immune-suppressing drugs used for organ transplant
patients; estrogens and oral contraceptives; certain calcium
channel blockers, used to treat hypertension; several
benzodiazepines, tranquilizers used to treat anxiety; many of the
statins, used to treat high cholesterol; loratadine, an
antihistamine; methadone, used to treat heroin addiction;
sildenafil, used to treat erectile dysfunction; sertraline, an
antidepressant; carbamazepine, an anti-seizure medicine; and
saquinavir, used to treat HIV infection.

As mentioned earlier, the interaction between these drugs and
grapefruit juice could be seen as a boon or bane depending on the
circumstances. For example, drinking a glass of the juice at the
same time as taking the drug sildenafil (Viagra) has allowed some
people to cut the dose of their medication in half while still
getting the same therapeutic effect. In an attempt to cut the cost
of the drug, many doctors have been actively recommending this
practice to their patients. In contrast, trying this procedure with
cyclosporine could be extremely risky because the drug has a high
degree of toxicity, especially when its blood levels are
excessively elevated.

Part of the problem with intentionally using grapefruit juice as
a “booster” to lower the therapeutic dose of certain medications is
that it is still not known which specific components of grapefruit
inhibit intestinal CYP3A4. Similar to what is often found with
botanical medicines, recent studies indicate that it is probably a
specific combination of ingredients that is responsible. (This
explains why orange juice, which contains many of the same
chemicals as grapefruit, does not have the same effect.) Because
grapefruit juice is not a standardized product, the active
ingredients—and the effect on drug metabolism—can vary from batch
to batch. Another issue is that people have different amounts of
CYP3A4 in their intestines. Those with lower amounts of the enzyme
are less susceptible to influence by grapefruit.

The complexities of this situation have led some doctors to
recommend that grapefruit juice be avoided by patients taking any
of the medications listed above. Rumor has it that some hospitals
have completely banned the juice from their kitchens. This
reactionary stance might be an easy way out, but it risks losing
something that is potentially of great value. Unfortunately, given
the strong possibility that other foods and herbs will be
discovered that can have similar effects to grapefruit, these kinds
of policies could eventually lead to a long list of banned foods.
In fact, one study found that 66 percent of twenty-one commonly
used medicinal herbs were CYP3A4 inhibitors, including goldenseal
(Hydrastis canadensis) and St. John’s wort (Hypericum perforatum).
Other studies have suggested that purple grape (Vitis labrusca) and
milk thistle (Silybum marianum) may also inhibit CYP3A4. Because
these studies were done in a test tube, the implications are
unclear; however, they do suggest the possibility that even more
interactions will be discovered.

Certainly, before we can make positive use of the
grapefruit/drug interaction, additional information is needed. When
more is understood about the active ingredients, it may be possible
to produce a standardized grapefruit product with consistent
potency. Sophisticated laboratory testing is on the horizon, and
someday this will be used to predict how an individual’s metabolism
might be affected by drinking biologically active foods such as
grapefruit or grape juice.

In the meantime, we simply have to accept the uncertainties
inherent in our current medical knowledge. According to Brahma
Singh, M.D., “Although there is a vast amount of literature, there
is still no rational scientific basis to predict the effect of food
for a particular chemical entity or a chemical class of therapeutic
agents.” Perhaps we can take some comfort in knowing that our
species has survived—and even thrived—despite dealing with these
kinds of complexities for many thousands of years.

Robert Rountree, M.D., is a physician in private practice in
Boulder, Colorado, where he practices integrative medicine. He is
co-author of 
Smart Medicine for a Healthier Child (Avery, 1994) and
Immunotics (Putnam, 2000), and is an Herb Research Foundation
advisory board member.

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